The long-term objective of this project is to develop a means by which cytotoxic T-lymphocytes can be induced in a naturally occurring lentiviral disease, equine infectious anemia, in order to determine and further characterize those responses involved in lentiviral control. Equine infectious anemia virus (EIAV) provides an excellent animal model to study this important genus of viruses which have emerged as important human and animal pathogens, responsible for persistent infections and often progressive disease. Characteristics such as marked, episodic, cell-free viremias and the high incidence of eventual control of EIAV infections allow for the dissection of immune mechanisms involved in this control. A retroviral vector expressing the env gene of EIAV will be constructed and utilized to induce cytotoxic T-lymphocytes (CTL) in horses. The nature of the CTL responses will then be investigated, specifically examining EIAV control by direct cytotoxic activity and/or the inhibition of EIAV replication by noncytolytic mechanisms. These horses will then be challenged with homologous and heterologous EIAV to determine if protective immune responses are elicited by the vector. This project will provide insight into those vector components which are successful at inducing specific, and possibly protective, immune responses and also evaluate mechanisms of CTL control of lentiviral infections. Taken together, these studies will provide information regarding immune response involve in lentiviral control and will provide a unique vector system whereby dissection of these responses, such as defining CTL epitopes, can be accomplished in future experiments.